Gratton, Jasmine;
Futema, Marta;
Humphries, Steve E;
Hingorani, Aroon D;
Finan, Chris;
Schmidt, Amand F;
(2023)
A Machine Learning Model to Aid Detection of Familial Hypercholesterolemia.
JACC: Advances
, 2
(4)
, Article 100333. 10.1016/j.jacadv.2023.100333.
Preview |
Text
1-s2.0-S2772963X23001072-main.pdf - Published Version Download (995kB) | Preview |
Abstract
Background: People with monogenic familial hypercholesterolemia (FH) are at an increased risk of premature coronary heart disease and death. With a prevalence of 1:250, FH is relatively common; but currently there is no population screening strategy in place and most carriers are identified late in life, delaying timely and cost-effective interventions. // Objectives: The purpose of this study was to derive an algorithm to identify people with suspected monogenic FH for subsequent confirmatory genomic testing and cascade screening. // Methods: A least absolute shrinkage and selection operator logistic regression model was used to identify predictors that accurately identified people with FH in 139,779 unrelated participants of the UK Biobank. Candidate predictors included information on medical and family history, anthropometric measures, blood biomarkers, and a low-density lipoprotein cholesterol (LDL-C) polygenic score (PGS). Model derivation and evaluation were performed in independent training and testing data. // Results: A total of 488 FH variant carriers were identified using whole-exome sequencing of the low-density lipoprotein receptor, apolipoprotein B, apolipoprotein E, proprotein convertase subtilisin/kexin type 9 genes. A 14-variable algorithm for FH was derived, with an area under the curve of 0.77 (95% CI: 0.71-0.83), where the top 5 most important variables included triglyceride, LDL-C, apolipoprotein A1 concentrations, self-reported statin use, and LDL-C PGS. Excluding the PGS as a candidate feature resulted in a 9-variable model with a comparable area under the curve: 0.76 (95% CI: 0.71-0.82). Both multivariable models (w/wo the PGS) outperformed screening-prioritization based on LDL-C adjusted for statin use. // Conclusions: Detecting individuals with FH can be improved by considering additional predictors. This would reduce the sequencing burden in a 2-stage population screening strategy for FH.
| Type: | Article |
|---|---|
| Title: | A Machine Learning Model to Aid Detection of Familial Hypercholesterolemia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jacadv.2023.100333 |
| Publisher version: | http://dx.doi.org/10.1016/j.jacadv.2023.100333 |
| Language: | English |
| Additional information: | Copyright © 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an Open Access article under the CC BY License (http://creativecommons.org/licenses/by/4.0/) . |
| Keywords: | FH; polygenic score; prediction; screening; UK Biobank |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10185735 |
Archive Staff Only
 |
View Item |
